Abstract
Gender medicine is the first step of personalized medicine and patient-centred care, an essential development to achieve the standard goal of a holistic approach to patients and diseases. By addressing the interrelation and integration of biological markers (i.e., sex) with indicators of psychological/cultural behaviour (i.e., gender), gender medicine represents the crucial assumption for achieving the personalized health-care required in the third millennium. However, ‘sex’ and ‘gender’ are often misused as synonyms, leading to frequent misunderstandings in those who are not deeply involved in the field. Overall, we have to face the evidence that biological, genetic, epigenetic, psycho-social, cultural, and environmental factors mutually interact in defining sex/gender differences, and at the same time in establishing potential unwanted sex/gender disparities. Prioritizing the role of sex/gender in physiological and pathological processes is crucial in terms of efficient prevention, clinical signs’ identification, prognosis definition, and therapy optimization. In this regard, the omics-approach has become a powerful tool to identify sex/gender-specific disease markers, with potential benefits also in terms of socio-psychological wellbeing for each individual, and cost-effectiveness for National Healthcare systems. “Being a male or being a female” is indeed important from a health point of view and it is no longer possible to avoid “sex and gender lens” when approaching patients. Accordingly, personalized healthcare must be based on evidence from targeted research studies aimed at understanding how sex and gender influence health across the entire life span. The rapid development of genetic tools in the molecular medicine approaches and their impact in healthcare is an example of highly specialized applications that have moved from specialists to primary care providers (e.g., pharmacogenetic and pharmacogenomic applications in routine medical practice). Gender medicine needs to follow the same path and become an established medical approach. To face the genetic, molecular and pharmacological bases of the existing sex/gender gap by means of omics approaches will pave the way to the discovery and identification of novel drug-targets/therapeutic protocols, personalized laboratory tests and diagnostic procedures (sex/gender-omics). In this scenario, the aim of the present review is not to simply resume the state-of-the-art in the field, rather an opportunity to gain insights into gender medicine, spanning from molecular up to social and psychological stances. The description and critical discussion of some key selected multidisciplinary topics considered as paradigmatic of sex/gender differences and sex/gender inequalities will allow to draft and design strategies useful to fill the existing gap and move forward.
Highlights
Our group has contributed for a long time to the disclosure of the genetics/pharmacogenetics bases of myocardial infarction [54,55,56,57,58,59], and very recently we summarized our previous efforts and patents [US2016363592 (A1); ITTO20130532 (A1)] in a Special Issue belonging to the “Novel Molecular Targets for Cardioprotection: The European Union (EU)-Cardioprotection Cost Action (CA16225)”, which suggest useful sex-oriented prognostic biomarkers [60]
A review paper analysing over 11,000 patients treated with immune checkpoint inhibitors in twenty randomized controlled trials, evidenced that the overall survival was consistently higher for men than for women, regardless of cancer histotype, line of treatment and type of administered drug [99]
Alzheimer’s disease (AD) is a multifactorial neurodegenerative disease and it represents the main form of dementia affecting patients, accounting for up to 80% of all cases in which sex, genetic, intellectual, as well as psychosocial factors might play a role in favouring cognitive decline [142]
Summary
Females were just one third of the enrolled patients in clinical trials performed between 2002 and 2007 to evaluate cardiovascular devices, and the number of recruited females did not increase over time [9] In another context, it has been demonstrated that the genomic profile of non-small-cell lung cancer patients had strong sex differences in signalling pathways [10], suggesting that prognostic biomarkers could be different and should be selectively used depending on sex. There has been a growing attention to sex-based differences in biology, genetics, biomedical sciences and general medicine, ranging from the cellular level to whole organs and organisms As expected, this process quickly led to the generation of new insights into diagnostic, prognostic and therapeutic issues, from basic research to the clinical level [17]. We critically discuss facts and mistakes with the aim of verifying whether and what we have learned from the past, and of filling the gap in the light of an emerging new personalized sex/gender-omics medicine
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